- Triflic acid-catalyzed metal-free synthesis of (: E)-2-cyanoacrylamides and 3-substituted azetidine-2,4-diones
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A TfOH-catalyzed highly efficient synthesis of biologically active (E)-2-cyanoacrylamides and 3-substituted azetidine-2,4-diones has been reported with 64-94% yields under metal-free conditions. The reaction proceeds through sequential Knoevenagel condens
- Rupanwar, Bapurao D.,Chavan, Santosh S.,Shelke, Anil M.,Suryavanshi, Gurunath M.
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supporting information
p. 6433 - 6440
(2018/04/23)
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- (E)-2-Cyano-3-(substituted phenyl)acrylamide analogs as potent inhibitors of tyrosinase: A linear β-phenyl-α,β-unsaturated carbonyl scaffold
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In this study, we synthesized (E)-2-cyano-3-(substituted phenyl)acrylamide (CPA) derivatives which possess a linear β-phenyl-α,β-unsaturated carbonyl scaffold and examined their inhibitory activities against tyrosinase. CPA analogs exerted inhibitory acti
- Son, Sujin,Kim, Haewon,Yun, Hwi Young,Kim, Do Hyun,Ullah, Sultan,Kim, Seong Jin,Kim, Yeon-Jeong,Kim, Min-Soo,Yoo, Jin-Wook,Chun, Pusoon,Moon, Hyung Ryong
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p. 7728 - 7734
(2015/12/20)
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- Regiospecific Mno2 catalyzed hydration of phenylmethylene malononitriles to cyanophenylacrylamides by oximes
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A novel and convenient method for the regiospecific hydration of phenylmethylene malononitriles to cyanoacrylamides was developed; Scope of the method and reaction conditions were optimized extensively, the method was found to be extremely successful in h
- Rauf, Abdul,Awan, Faisal Saleem,Mumtaz, Saira,Sharif, Ahsan,Ahmed, Ejaz,Arshad, Muhammad,Kausar, Farzana,Yasmin, Ghazala,Qureshi, Ashfaq Mahmood
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experimental part
p. 728 - 731
(2012/08/07)
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- Arylcyanoacrylamides as inhibitors of the Dengue and West Nile virus proteases
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The 3-aryl-2-cyanoacrylamide scaffold was designed as core pharmacophore for inhibitors of the Dengue and West Nile virus serine proteases (NS2B-NS3). A total of 86 analogs was prepared to study the structure-activity relationships in detail. Thereby, it turned out that the electron density of the aryl moiety and the central double bond have a crucial influence on the activity of the compounds, whereas the influence of substituents of the amide residue is less relevant. The para-hydroxy substituted analog was found to be the most potent inhibitor in this series with a Ki-value of 35.7 μM at the Dengue and 44.6 μM at the West Nile virus protease. The aprotinin competition assay demonstrates a direct interaction of the inhibitor molecule with active centre of the Dengue virus protease. The target selectivity was studied in a counterscreen with thrombin and found to be 2.8:1 in favor of DEN protease and 2.3:1 in favor of WNV protease, respectively.
- Nitsche, Christoph,Steuer, Christian,Klein, Christian D.
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experimental part
p. 7318 - 7337
(2012/01/05)
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- Solvent-free Knoevenagel condensations and Michael additions in the solid state and in the melt with quantitative yield
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Numerous Knoevenagel condensations of solid or liquid aromatic aldehydes are performed with four barbituric acids, Meldrum's acid, dimedone, cyanoacetamide, malodinitrile and methyl cyanoacetate in stoichiometric mixtures of the solids or of stoichiometri
- Kaupp, Gerd,Naimi-Jamal, M. Reza,Schmeyers, Jens
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p. 3753 - 3760
(2007/10/03)
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- Structural studies on bioactive compounds. 32. Oxidation of tyrphostin protein tyrosine kinase inhibitors with hypervalent iodine reagents
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Hydroxylated styrenes (tyrphostins) undergo oxidation by hypervalent iodine oxidants such as [(diacetoxy)iodo]benzene (DAIB) to give a range of products depending on the structure of the phenolic substrate, the solvent, the oxidant stoichiometry, and the purification strategy. Conditions have been developed to modify the phenolic component of the tyrphostin without affecting the appended substituted-vinyl moiety. Novel products include: unstable 2-acyloxy-2-methoxy-4-(substituted-vinyl)cyclohexadienones and their rearrangement products 2-acyloxy-4-hydroxy-3-methoxy-1-(substituted- vinyl)benzenes; phenyliodoniophenolates and their rearrangement products iodophenoxytyrphostins; and 3,3'-dialkoxy-2,2'-dihydroxy-5,5'-di(substituted- vinyl)biphenyls. None of these oxidation products displayed enhanced activity in vitro in the NCI 60-cell line panel or in a panel of human breast cancer cell lines, compared to their tyrphostin precursors. The inhibitory activity of three representative tyrphostins (3e,n, 28) was not modulated by aerobic/anaerobic conditions in MCF-7 and MDA 468 cells and was independent of EGFR status in clones of ZR75B cells transfected with this receptor. Basal growth of MCF-7 cells was unaffected by co-administration of the growth factors EGF, TGF-α, IGF-I, and IGF-II, and the new agents did not inhibit EGFR and c-erbB2 autophosphorylation in cell lysates from MDA 468 or SkBr3 cells, respectively, suggesting that receptor tyrosine kinases are not targets for these compounds. Growth stimulation by the tyrphostin 3n in the ER+ breast cell lines MCF-7, T47D, and ZR75-1 was abolished by 1 μM tamoxifen, suggesting that this compound has estrogen agonist activity.
- Wells, Geoffrey,Seaton, Angela,Steven, Malcolm F. G.
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p. 1550 - 1562
(2007/10/03)
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- Knoevenagel condensation in heterogeneous phase catalyzed by IR radiation and Tonsil Actisil FF
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Infrared radiation promoted the synthesis of benzylidenemalononitriles, benzylidenecyanoacetamides and benzylidenecyanoacetic acids by condensation of aromatic aldehydes with the corresponding active methylene compound in the presence of Tonsil Actisil FF, without solvent. Mass of catalyst, solvent, and reaction time were assessed in order to improve the efficiency of this process.
- Obrador, Esteban,Castro, Martin,Tamariz, Joaquin,Zepeda, Gerardo,Miranda, Rene,Delgado, Francisco
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p. 4649 - 4663
(2007/10/03)
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- Knoevenagel condensation catalyzed by USY zeolite
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The Knoevenagel condensation of substituted benzaldehydes with active methylene compounds was performed very efficiently by using a USY (ultrastable Y) zeolite as heterogeneous catalyst.
- Wang,Ma, YuDao,Zuo, BoJun
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p. 4107 - 4110
(2007/10/03)
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- Bicyclic compounds as ring-constrained inhibitors of protein-tyrosine kinase p56(lck)
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A study was undertaken to prepare inhibitors of the lymphocyte protein- tyrosine kinase p56(lck). Using the known p56(lck) inhibitor 3,4-dihydroxy- α-cyanocinnamamide (4) as a lead compound, bicyclic analogues were designed as conformationally constrained
- Burke Jr.,Lim,Marquez,Li,Bolen,Stefanova,Horak
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p. 425 - 432
(2007/10/02)
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- Polyhydroxylated phenylacrylic acid derivatives as new anti-tumor agents
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Preliminary evidence indicates that antitumor agents containing the o-dihydroxybenzene moiety exhibit enhanced antitumor activity toward malignant cells of high oxidative potential, such as melanoma cells. Based on this consideration, 11 hydroxybenzene acrylic acid derivatives of differing redox potential were prepared as potential substrates for the melanoma specific enzyme tyrosinase, that might exhibit general antitumor activity and enhanced cytotoxicity toward melanoma cells. Five of these compounds [α-cyano-β-(4-hydroxyphenyl)-, α-cyano-β-(3,4-dihydroxyphenyl)-, and α-cyano-β-(3,4,5-trihydroxyphenyl)acrylic acid (THPPA), and 3,4-dihydroxy- and 3,4,5-trihydroxybenzalcyanoacetamide] were found to be substrates for tyrosinase with k(m) values from 0.08 to 4.13 mM and V(max) values from 0.18 to 3.02. These data indicate that as the number of hydroxy groups increases, the rate of oxidation increases, and that cyanoamides were faster reacting than corresponding cyanoacids, with dicyanides the least reactive. In contrast, cyanoamides were less effective as substrates than cyanoacids. In vitro studies showed all but two compounds were active against L1210 (IC50 range 21-980 μM), SK-MEL-28 (IC50 range 54-950 μM), and SK-MEL-30-3 (IC50 range 54-190 μM). Only THPPA was active in vivo against L1210 and B-16 melanoma.
- Hussoin,FitzGerald,Wick
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p. 416 - 418
(2007/10/02)
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- Tyrphostins I: Synthesis and Biological Activity of Protein Tyrosine Kinase Inhibitors
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A novel class of low molecular weight proteine kinase inhibitors is described.These compounds consitute a systematic series of molecules with a progressive increase in affinity toward the substrate site of the EGF receptor kinase domain.These competitive inhibitors also effectively block the EGF-dependent autophosphorylation of the receptor.The potent EGF receptor kinase blockers examined were found to competitively inhibit the homologous insulin receptor kinase at 102-103 higher inhibitor concentrations in spite of the significant homology between these protein tyrosine kinases.These results demonstrate the ability to synthesize selective tyrosine kinase inhibitors.The most potent EGF receptor kinase inhibitors also inhibit the EGF-dependent proliferation of A431/clone 15 cells with little or no effect on EGF independent cell growth.These results demonstrate the potential use of protein tyrosine kinase inhibitors as selective antiproliferative agents for proliferative diseases caused by the hyperactivity of protein tyrosine kinases.We have suggested the name "tyrphostins" for this class of antiproliferative compounds which act as protein tyrosine kinase blockers.
- Gazit, Aviv,Yaish, Pnina,Gilon, Chaim,Levitzki, Alexander
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p. 2344 - 2352
(2007/10/02)
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